Applied Radiology

Diagnosis

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, strokes)

Findings

Axial-FLAIR and diffusion-weighted images as well as magnetic resonance (MR) spectroscopic imaging data are provided. The FLAIR image demonstrates bilateral cortical- and subcortical-signal abnormality within the temporal and parietal lobes with swollen gyri and compressed sulci. Signal abnormality is much worse on the right. Diffusion-weighted imaging demonstrates restricted diffusion affecting the cortex in the same distribution. MR spectroscopy spectra sampling the area of FLAIR-signal abnormality demonstrate a markedly elevated lactate doublet at a TE of 30 ms, which inverts at a longer TE of 130 ms.

Discussion

Mitochondrial myopathy, encephalopathy, lactic acidosis, strokes or MELAS Syndrome represents a group of genetic disorders, which occur secondary to mutations in mitochondrial DNA. Therefore, there is exclusive maternal inheritance. The genetic mutation results in abnormal protein synthesis, which affects the aerobic respiratory chain, ultimately resulting in a decrease in NADH+ and NAD+. Because there is malfunctioning aerobic metabolism, the body shifts to anaerobic metabolism, which results in a buildup of neurotoxic lactic acid.

Patients with MELAS present at an average age of 15 years with 90% of patients presenting before the age of 40. Common signs and symptoms include seizures, stroke-like episodes, muscle weakness, sensineural hearing loss, exercise intolerance, headaches, nausea/vomiting, short stature, and cognitive deficits. The course of MELAS is progressive with acute exacerbations.

Computed tomography (CT) is not particularly useful for MELAS and may only show symmetric basal ganglia calcifications. MR imaging features of acute MELAS include swollen gyri and compressed sulci with T2/FLAIR hyperintensity within the cortex and subcortical white matter, most commonly parietooccipital and temporoparietal. Diffusion-weighted imaging demonstrates restricted diffusion in the same distribution. Classically there is “shifting spread” of the affected regions during acute episodes with appearance, disappearance, and reappearance elsewhere. Contrast-enhanced images may show gyral enhancement during acute episodes. Chronic MELAS will show cortical atrophy involving the affected portions of the temporal, parietal, and occipital lobes as well as basal ganglia atrophy and hyperintensity.

Spectral imaging usually, but not always, demonstrates an elevated lactate doublet at 1.3 ppm. Confirmation that the peak represents lactate can be accomplished by using a long TE (approximately 135 ms), which will invert the doublet. A short TE of 30 ms will show an upright lactate doublet.

Elevated lactate levels are often found in CSF as well as blood. Often muscle biopsy is used to confirm the diagnosis of MELAS by identifying ragged red fibers as well as specific mitochondrial enzymes.

1. Castillo M, Kwock L, Green C. MELAS Syndrome: Imaging and proton MR spectroscopic findings. AJNR Am J Neuroradiol. 1995;16:233–239.
2. Kim IO, JH Kim, WS Kim et al. Mitochondrial myopathy-encephalopathy-lactic acidosis-and stroke-like episodes (MELAS) syndrome: CT and MR findings in seven children. Am. J. Roentgenol. 1996;166: 641-645.